CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) is a randomized controlled trial (RCT) comparing 2 outcomes in hospitalized patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. The primary outcome was hospital Length of Stay (LOS) and the secondary outcome was the Re-Admission Rate (RAR) 30 days after discharge. The trial setting was the Institute of Living at Hartford Hospital. CYP2D6 genotyping was implemented to detect common polymorphisms resulting in an enzyme with sub-normal, normal or supra-normal function. The electronic medical record (EMR) was utilized to transmit clinically actionable drug prescribing guidance based on the patient's CYP2D6 genotype to the physician. The RCT recruited 1500 patients, genotyped CYP2D6 in 1459, and randomized 477 to standard therapy (Group S), for whom treatment-as-usual guidance was delivered without consideration of patient CYP2D6 genotype, and 982 to genetically-guided therapy (Group G) where CYP2D6-based treatment recommendations were provided via EMR to physicians. For inpatients in Group G whose CYP2D6 function was sub- or supra-normal, medications primarily metabolized by the CYP2D6 enzyme were proscribed. The RCT developed a database of potential benefit to the field. The genetic, pharmacologic and clinical information is being simultaneously published. Results did not reveal differences in LOS or RAR between Group G and Group S, but confounders may have obscured the effects of pharmacogenetic guidance. We present strategies to assess effects of pharmacogenetic guidance on the most vulnerable patients at either extreme of CYP2D6 function treated with multiple psychotropics.
Keywords: CYP2D6; Major depressive disorder; RCT; hospital length of stay; hospital readmission rate; pharmacogenetics; psychotropics.
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